LncRNA HOTAIR sponges miR-301a-3p to promote glioblastoma proliferation and invasion through upregulating FOSL1.
LncRNA HOTAIR sponges miR-301a-3p to promote glioblastoma proliferation and invasion through upregulating FOSL1.
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DOI：
10.1016/j.cellsig.2022.110306
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发表时间：
2022-06
影响因子：
4.8
通讯作者：
Liu, Mingli
中科院分区：
文献类型：
--
作者：
Guo, Shanchun;King, Pendelton;Liang, Emily;Guo, Alyssa A.;Liu, Mingli
胶质母细胞瘤是最致命的脑肿瘤之一，与预后差和总生存期极短有关。我们先前报道过高表达的瞬时受体电位通道TRPM7是胶质母细胞瘤的重要调节因子。越来越多的证据表明，长非编码RNA(LncRNAs)在胶质瘤的发生发展中起着重要作用。然而，TRPM7介导的LncRNA，Hox转录的反义基因间RNA(HOTAIR)在胶质瘤中的作用尚不清楚。在这项研究中，发现HOTAIR的表达受到TRPM7的正向调节，在胶质瘤组织中显著上调，对胶质瘤患者来说是一个不良的预后因素。此外，HOTAIR表达降低阻碍了胶质瘤细胞的增殖和侵袭。在机制上，HOTAIR与miR-301a-3p直接相互作用，miR-301a-3p的下调有效地逆转了siRNA HOTAIR对FOSL1的抑制，提示HOTAIR通过海绵miR-301a-3p正向调节FOSL1水平，在脑胶质瘤的发生发展中起一定作用。与HOTAIR的作用不同，miR-301a-3p单独作为肿瘤抑制因子可以降低胶质瘤细胞的活力和迁移/侵袭。与HOTAIR的作用一致，FOSL1在脑胶质瘤的发病机制中发挥了致癌基因的作用，在脑胶质瘤组织中高表达，并被认为是脑胶质瘤患者预后不良的因素。从机制上讲，siRNA FOSL1抑制FOSL1有效地挽救了miR-301a-3p抑制剂在胶质瘤发病机制中引起的致癌表型。
Glioblastoma, one of the most fatal brain tumors, is associated with a dismal prognosis and an extremely short overall survival. We previously reported that the overexpressed transient receptor potential channel TRPM7 is an essential glioblastoma regulator. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in glioma’s initiation and progression. However, the function of lncRNA, HOX transcript antisense intergenic RNA (HOTAIR) mediated by TRPM7 in glioma remains unclear. In this study, HOTAIR expression was found to be positively regulated by TRPM7, significantly upregulated in glioma tissues, and is a poor prognosis factor for glioma patients. Moreover, reduced HOTAIR expression impeded the proliferation and invasion of glioma cells. Mechanistically, HOTAIR directly interacted with miR-301a-3p, and downregulation of miR-301a-3p efficiently reversed FOSL1 suppression induced by siRNA HOTAIR, which implied that HOTAIR positively regulated FOSL1 level through sponging miR-301a-3p and played an oncogenic role in glioma progression. In contrast to HOTAIR’s role, miR-301a-3p alone served as a tumor suppressor to decrease glioma cell viability and migration/invasion. In agreement with HOTAIR’s role, FOSL1 functioned as a tumorigenic gene in glioma pathogenesis, which was highly expressed in glioma tissues, and was shown to be an unfavorable prognostic factor for glioma patients. Mechanically, FOSL1 inhibition by siRNA FOSL1 efficiently rescued the oncogenic-like phenotypes caused by the miR-301a-3p inhibitor in glioma pathogenesis.
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